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991.
992.
Youhei Kitamura Masahiro Koide Yoshiki Akakabe Kiyonari Matsuo Yoshiaki Shimoda Yuka Soma Takehiro Ogata Tomomi Ueyama Satoaki Matoba Hiroyuki Yamada Koji Ikeda 《The Journal of biological chemistry》2014,289(5):2788-2800
PI3K/Akt signaling plays an important role in the regulation of cardiomyocyte death machinery, which can cause stress-induced cardiac dysfunction. Here, we report that apoptosis regulator through modulating IAP expression (ARIA), a recently identified transmembrane protein, regulates the cardiac PI3K/Akt signaling and thus modifies the progression of doxorubicin (DOX)-induced cardiomyopathy. ARIA is highly expressed in the mouse heart relative to other tissues, and it is also expressed in isolated rat cardiomyocytes. The stable expression of ARIA in H9c2 cardiac muscle cells increased the levels of membrane-associated PTEN and subsequently reduced the PI3K/Akt signaling and the downstream phosphorylation of Bad, a proapoptotic BH3-only protein. When challenged with DOX, ARIA-expressing H9c2 cells exhibited enhanced apoptosis, which was reversed by the siRNA-mediated silencing of Bad. ARIA-deficient mice exhibited normal heart morphology and function. However, DOX-induced cardiac dysfunction was significantly ameliorated in conjunction with reduced cardiomyocyte death and cardiac fibrosis in ARIA-deficient mice. Phosphorylation of Akt and Bad was substantially enhanced in the heart of ARIA-deficient mice even after treatment with DOX. Moreover, repressing the PI3K by cardiomyocyte-specific expression of dominant-negative PI3K (p110α) abolished the cardioprotective effects of ARIA deletion. Notably, targeted activation of ARIA in cardiomyocytes but not in endothelial cells reduced the cardiac PI3K/Akt signaling and exacerbated the DOX-induced cardiac dysfunction. These studies, therefore, revealed a previously undescribed mode of manipulating cardiac PI3K/Akt signaling by ARIA, thus identifying ARIA as an attractive new target for the prevention of stress-induced myocardial dysfunction. 相似文献
993.
Juan C. Zapata Marco Goicochea Yuka Nadai Lindsay M. Eyzaguirre Jean K. Carr Luke J. Tallon Lisa Sadzewicz Garry Myers Claire M. Fraser Qi Su Mahmoud Djavani Igor S. Lukashevich Maria S. Salvato 《Journal of virology》2014,88(6):3058-3066
The attenuated Lassa vaccine candidate ML29 is a laboratory-produced reassortant between Lassa and Mopeia viruses, two Old World arenaviruses that differ by 40% in nucleic acid sequence. In our previous studies, ML29 elicited sterilizing immunity against Lassa virus challenge in guinea pigs and marmosets and virus-specific cell-mediated immunity in both simian immunodeficiency virus (SIV)-infected and uninfected rhesus macaques. Here, we show that ML29 is stable after 12 passages in vitro without losing its plaque morphology or its attenuated phenotype in suckling mice. Additionally, we used deep sequencing to characterize the viral population comprising the original stock of ML29, the stock of ML29 after 12 passages in Vero cells, and the ML29 isolates obtained from vaccinated animals. Twenty-seven isolates bore approximately 77 mutations that exceeded 20% of the single-nucleotide polymorphism (SNP) changes at any single locus. Of these 77 mutations, 5 appeared to be host specific, for example, appearing in mice but not in primates. None of these mutations were reversions of ML29 to the sequences of the parental Lassa and Mopeia viruses. The host-specific mutations indicate viral adaptations to virus-host interactions, and such interactions make reasonable targets for antiviral approaches. Variants capable of chronic infection did not emerge from any of the primate infections, even in immune-deficient animals, indicating that the ML29 reassortant is reasonably stable in vivo. In conclusion, the preclinical studies of ML29 as a Lassa virus vaccine candidate have been advanced, showing high levels of protection in nonhuman primates and acceptable stability both in vitro and in vivo. 相似文献
994.
995.
Makabe H Kimura Y Higuchi M Konno H Murai M Miyoshi H 《Bioorganic & medicinal chemistry》2006,14(9):3119-3130
A convergent stereoselective synthesis of (4R,15R,16R,21S)- and (4R,15S,16S,21S)-rollicosin and squamostolide was accomplished via a Pd-catalyzed cross-coupling reaction. The inhibitory activity of these compounds was examined with bovine heart mitochondrial NADH-ubiquinone oxidoreductase. These compounds showed a remarkably weak inhibitory activity compared to ordinary acetogenins such as bullatacin. Our results indicate that to maintain potent inhibitory effect, the hydroxylated lactone cannot substitute for the hydroxylated mono- or bis-THF rings with a long alkyl chain that can be seen in ordinary acetogenins. 相似文献
996.
Kusumoto K Uto H Hayashi K Takahama Y Nakao H Suruki R Stuver SO Ido A Tsubouchi H 《Cytokine》2006,34(1-2):24-31
We investigated the effects of polymorphisms in interleukin (IL)-10 and tumor necrosis factor (TNF)-alpha on the natural course of hepatitis C virus (HCV) infection in a community-based population in Japan. A total of 460 anti-HCV antibody seropositive individuals were classified into two groups, those who were positive or negative for HCV RNA. In HCV RNA-positive individuals with at least four annual alanine aminotransferase (ALT) measurements taken between 1993 and 2003, 74 exhibited persistently normal ALT levels, while 211 had one or more elevated ALT level tests. We examined the relationships between polymorphisms in the genes encoding IL-10 (-1082, -819, -592) or TNF-alpha (-308, -238) and HCV clearance, ALT abnormalities, or serum level of type IV collagen 7S, a marker of hepatic fibrosis. These polymorphisms were equally distributed among the patient subgroups with differential HCV RNA clearances or ALT abnormalities. Serum levels of type IV collagen 7S, however, were significantly higher in individuals with an A at position -238 or -308 in the TNF-alpha gene promoter than in individuals lacking these polymorphisms. We conclude that, while the relationships between inherited variations in IL-10 or TNF-alpha expression are not associated with alterations in HCV clearance or ALT levels, TNF-alpha polymorphisms may be associated with hepatic fibrosis. 相似文献
997.
Ebihara Shizufumi Tomida Shigeru Mamiya Takayoshi Sakamaki Hirotake Miura Masami Aosaki Toshihiko Masuda Masao Niwa Minae Kameyama Tsutomu Kobayashi Junya Iwaki Yuka Imai Saki Ishikawa Akira Abe Kuniya Yoshimura Takashi Nabeshima Toshitaka 《Sleep and biological rhythms》2010,8(2):114-119
Sleep and Biological Rhythms - CS mice exhibit several distinct phenotypes of circadian behavioral rhythms and sleep properties. Because many mental illnesses are associated with abnormalities in... 相似文献
998.
Kobayashi H Azumi M Kimura Y Sato K Aoki N Kimura S Honma M Iizuka H Tateno M Celis E 《Cancer immunology, immunotherapy : CII》2009,58(6):931-940
Background Focal adhesion kinase (FAK) is a ubiquitously expressed non-receptor tyrosine kinase involved in cancer progression and metastasis
that is found overexpressed in a large number of tumors such as breast, colon, prostate, melanoma, head and neck, lung and
ovary. Thus, FAK could be an attractive tumor associated antigen (TAA) for developing immunotherapy against a broad type of
malignancies. In this study, we determined whether predicted T cell epitopes from FAK would be able to induce anti-tumor immune
cellular responses.
Methods To validate FAK as a TAA recognized by CD4 helper T lymphocytes (HTL), we have combined the use of predictive peptide/MHC
class II binding algorithms with in vitro vaccination of CD4 T lymphocytes from healthy individuals and melanoma patients.
Results Two synthetic peptides, FAK143–157 and FAK1,000–1,014, induced HTL responses that directly recognized FAK-expressing tumor cells and autologous dendritic cells pulsed with FAK-expressing
tumor cell lysates in an HLA class II-restricted manner. Moreover, since the FAK peptides were recognized by melanoma patient’s
CD4 T cells, this is indicative that T cell precursors reactive with FAK already exist in peripheral blood of these patients.
Conclusions Our results provide evidence that FAK functions as a TAA and describe peptide epitopes that may be used for designing T cell-based
immunotherapy for FAK-expressing cancers, which could be used in combination with newly developed FAK inhibitors. 相似文献
999.
Isolation and characterization of fructophilic lactic acid bacteria from fructose-rich niches 总被引:1,自引:0,他引:1
Fourteen strains of fructophilic lactic acid bacteria were isolated from fructose-rich niches, flowers, and fruits. Phylogenetic analysis and BLAST analysis of 16S rDNA sequences identified six strains as Lactobacillus kunkeei, four as Fructobacillus pseudoficulneus, and one as Fructobacillus fructosus. The remaining three strains grouped within the Lactobacillus buchneri phylogenetic subcluster, but shared low sequence similarities to other known Lactobacillus spp. The fructophilic strains fermented only a few carbohydrates and fermented d-fructose faster than d-glucose. Based on the growth characteristics, the 14 isolates were divided into two groups. Strains in the first group containing L. kunkeei, F. fructosus, and F. pseudoficulneus grew well on d-fructose and on d-glucose with pyruvate or oxygen as external electron acceptors, but poorly on d-glucose without the electron acceptors. Strains in this group were classified as “obligately” fructophilic lactic acid bacteria. The second group contained three unidentified strains of Lactobacillus that grew well on d-fructose and on d-glucose with the electron acceptors. These strains grew on d-glucose without the electron acceptors, but at a delayed rate. Strains in this group were classified as facultatively fructophilic lactic acid bacteria. All fructophilic isolates were heterofermentative lactic acid bacteria, but “obligately” fructophilic lactic acid bacteria mainly produced lactic acid and acetic acid and very little ethanol from d-glucose. Facultatively fructophilic strains produced lactic acid, acetic acid and ethanol, but at a ratio different from that recorded for heterofermentative lactic acid bacteria. These unique characteristics may have been obtained through adaptation to the habitat. 相似文献
1000.
Matsushita-Ishiodori Y Kuwabara R Sakakoshi H Endoh T Ohtsuki T 《Bioconjugate chemistry》2011,22(11):2222-2226
RNA interference (RNAi) is being widely explored as a tool in functional genomics and tissue engineering, and in the therapy of intractable diseases, including cancer and neurodegenerative diseases. Recently, we developed a photoinducible RNAi method using photosensitizing carrier proteins, named CLIP-RNAi (CPP-linked RBP-mediated RNA internalization and photoinduced RNAi). Novel carrier proteins were designed for this study to establish a highly efficient delivery system for small interfering RNA (siRNA) or short hairpin RNA (shRNA) and to demonstrate light-dependent gene silencing. In addition, the results suggested that the dissociation of the siRNA (or shRNA) from carrier proteins in the cytoplasm is a critical event in CLIP-RNAi-mediated gene silencing. 相似文献